Fontan Deterioration in Pediatric Cardiac Surgeon's View

Sejong General Hospital

Fontan Deterioration in Pediatric Cardiac Surgeon’s View

세종병원 흉부외과 이창하 Sejong General Hospital

Fontan deterioration

Failing Fontan Failed Fontan Fontan Failure Sejong General Hospital Fontan operation

‘This procedure is not an anatomical correction, which would require the creation of a right ventricle, but a procedure of physiological pulmonary blood flow restoration, with suppression of right and left blood mixing’

(F. Fontan and E. Baudet, Thorax, 1971) Sejong General Hospital

1975 - 1988 334 patient underwent Fontan procedure under optimal conditions Sejong General Hospital Outcome after a "perfect" Fontan operation Survival After Perfect Fontan Operation

* The appreciable late hazard (instantaneous risk of death at each moment in time after the operation) gradually began to increase about 6 years after surgery. Sejong General Hospital Outcome after a "perfect" Fontan operation Functional Status Sejong General Hospital

The inference is that the premature decline in survival and functional status and the late rise in hazard function are from the Fontan state per se and that the Fontan operation is, therefore, palliative but not curative. Sejong General Hospital Fontan circulation -Physiologic & anatomic sequelae-

Exclusion of ventricle from pulmonary circulation

Turbulence & energy loss in the flow

Flow stasis, thrombosis, partial obstruction

Increase in systemic venous pressure

Increase in production of lymph Generalized edema Recurrent effusion Protein-losing enteropathy (PLE) Loss of albumin, antibodies, lymphocytes

Decrease in oncotic pressure Fontan failure Sejong General Hospital Fontan circulation -Physiologic & anatomic sequelae-

Exclusion of ventricle from pulmonary circulation

Turbulence & energy loss in the flow

Flow stasis, baffle thrombus Increase in systemic venous pressure

Repeated subclinical pulmonary emboli Elevated RA pressure

Increasing pulmonary vascular hypertension RA dilatation

Inefficient flow dynamics

Classic Glenn procedure Direct compression of pulmonary veins

Pulmonary AV fistulas Increasing pulmonary resistance

cyanosis Fontan failure Sejong General Hospital Fontan circulation -Systemic ventricular failure-

RA enlargement Increased RA pressure

Atrial arrhythmias Coronary sinus hypertension

Loss of synchrony Decreased myocardial perfusion

Ventricular diastolic dysfunction

Systemic ventricular dilatation & failure

Persisting or reoccurring cyanosis Sejong General Hospital Surgical modifications

• Not original Fontan or its modifications

• deLeval (1988)

– ‘Lateral wall’ TCPC; experimentally & clinically to be hemodynamically more efficient • Early 1990, extracardiac conduit Fontan procedure Sejong General Hospital Further surgical modifications

• Prior volume unloading via superior cavopulmonary connection (i.e. bidirectional Glenn, hemi-Fontan operation)

• Fenestration

• Better myocardial preservation techniques Sejong General Hospital

1995-2002 70 Fontan procedures 37 LT / 33 ECC Operative mortality 2.8% Survival at 5yr; 97% for LT, 91% for ECC, p = 0.4 Sejong General Hospital

1990-2004 162 Fontan procedures 49 ECC / 113 LT Overall operative mortality 1.8% Survival at 5yr; 90% EC, 95% LT, p = 0.08 Sejong General Hospital

Outcomes of current practice

Extracardiac conduit Fontan

Sejong experiences Sejong General Hospital Patients

Aug. 1996 ~ Aug. 2006 200 patients with extracardiac Fontan Op. Age : median 3.4Y (16M~35.7Y) Previous Op. before BCPS 94.0% (188) Staged Op. 89.5% (179) Fenestration 42.5% (85) Sejong General Hospital Overall Survival

100 92.4 ±±± 2.1% at 10Y 90

50 Mean FU of 52.4 mon(18d-120mon) 40 Hospital Death 3.0%(n=6) 30 Late Death 3.6%(n=7) Cumulative survival (%) survival Cumulative 20

0 0 10 20 30 40 50 60 70 80 90 100 110 120 Follow up duration (months) Sejong General Hospital Freedom from Reoperation

100

90 82.4 ±4.1% at 10Y

20 Freedom from reoperation (%) from reoperation Freedom 10 0 0 10 20 30 40 50 60 70 80 90 100 110 120 Follow up duration (months) Sejong General Hospital Reoperation • Reoperations 24(12%)

Reoperation Conduit revision 7 Fenestration 6 AV valve operation 5 PPM insertion 5 PA angioplasty 4 HV-azygos v 3 Other: Atrial septectomy(1),Azygos v-LPA(1),CS unroofing(1),LVOTO relieve(1) Sejong General Hospital Freedom from Arrhythmia 100 Late Arrhythmia, 85.1 ±±±4.4% at 10Y

Overall Arrhythmia, 79.8 ±±±3.7% at 10Y

505050 Freedom from arrhythmia (%) from arrhythmia Freedom

000505050 100 Follow up duration (months) Sejong General Hospital Arrhythmia

Type Overall Early Late Bradyarrhythmia 26 10 13 SN dysfunction 13 5 8 PPM 12 (3) 5 4 SN dysfunction 9 (3) 3 3 AV block 3 2 1 Sinus bradycardia 1 0 1 Tachyarrhythmia 10 7 3 PSVT 8 5 3 AF 2 2 0 JET 1 1 0 Total 32/200 15/200 15/194 (16.0%) (7.5%) (7.7%) Sejong General Hospital Freedom from Thromboembolism

92.9 ± 1.9% at 10Y 100

60 Incidence 13 / 200 (6.5%) 50 Before discharge 8 / 13 (61.5%) 40 Within 1year 11 / 13 (84.6%) 30

10 Freedom from thromboembolism (%) Freedom 0 0 10 20 30 40 50 60 70 80 90 100 110 120 Follow up duration (months) Sejong General Hospital Protein-losing Enteropathy (n=5) Recovery 3 Death 2 Reversal of protein-losing enteropathy with calcium replacement in a patient after Fontan operation.

Case

SJ Kim et al. Ann ThoracThorac surgsurg 2004;77:1456 2004;77:14562004;77:1456----7777 Sejong General Hospital

Surgical reinterventions following Fontan procedure Sejong General Hospital

1995-2001 123 procedures in 71 patients Median time from Fontan to reoperation 3.6yr Sejong General Hospital Surgical reinterventions following Fontan procedure

Petko et al. European Journal of Cardio-thoracic Surgery 24 (2003) 255–259 Sejong General Hospital Surgical reinterventions following Fontan procedure

• Pacemaker insertion (n = 38) • Hepatic vein reinclusion (n = 16) • Fontan revision (n = 13) • Heart transplantation (n = 9) • Fenestration creation/enlargement (n = 5) • AVV repair/replacement (n = 7)

Petko et al. European Journal of Cardio-thoracic Surgery 24 (2003) 255–259 Sejong General Hospital Surgical reinterventions following Fontan procedure

• Other procedures – Placement of a pericardial window for pericardial drainage – Pleural drainage for late effusions – Peripheral thrombectomy – Reconstruction of discontinuous pulmonary arteries – Repair of Fontan baffle leak – Takedown of the Fontan circulation to a superior cavopulmonary connection

Petko et al. European Journal of Cardio-thoracic Surgery 24 (2003) 255–259 Sejong General Hospital 10-year survival after Fontan-type operation

Number of Years of Survival (%) patients operation Fontan (1990) 334 1975-1988 69%

Driscoll (1992) 352 1973-1984 70%

Cetta (1992) 339 1987-1992 81%

Gentles (1997) 500 1973-1991 79%

Weipert (2004) 162 1978-1995 83%

Giannico (2006) 221 1988-2003 85% Sejong General Hospital

1988-2003 221 patient underwent extracardiac Fontan 193 early survivors Median F/U 50mo (1 -179mo) Sejong General Hospital Outcome of 193 survivors (mean 63mo, median 50mo)

77%

Giannico et al. JACC 47 (2006) 2065–73 Sejong General Hospital Late Fontan failure - Death, takedown, or heart transplantation -

94.2% at 10 years 92.2% at 15 years

Giannico et al. JACC 47 (2006) 2065–73 Sejong General Hospital Failing Fontan circulation

Fontan circulation Dysrhythmias Thromboembolism PLE Anatomic problems – AVVR, SAS Ventricular dysfunction Elevated PVR Collateralization – systemic venous Pulmonary AV fistulas …

Persisting or reoccurring cyanosis Exercise intolerance

Late death Deteriorated Takedown of Fontan pathway to AP shunt or BCPS Fontan circulation Fontan conversion Heart transplantation Sejong General Hospital

Failing Fontan circulation

Fontan conversion vs. Heart transplantation Sejong General Hospital Failed Fontan

Fontan conversion vs. transplantation

(Mavroudis et al. J Thorac Cardiovasc Surg 2001;122:863-71) Sejong General Hospital Fontan conversion vs. transplantation

• The presence of substrates that can be repaired

– A valve lesion

• AV valve or aortic valve – An obstructive lesion

• Baffling obstruction

• Pulmonary vein compression – Ventricular dysfunction associated with arrhythmogenic or anatomic substrates Sejong General Hospital Fontan conversion vs. transplantation

• Isolated systemic ventricular dysfunction

– Ventricular dysfunction

• VEDP ≥ 12mmHg • Underloaded ventricle – Low cardiac output – Poor transit of systemic venous blood into & through the lungs • PLE • NYHA class IV heart failure Sejong General Hospital

이창하3 Fontan conversion 슬라이드 38 이창하3 heart failure in children and young adult 참조하고 있음 이창하, 2007-04-12 Sejong General Hospital Surgical management protocol

• Takedown of old Fontan connection • Creation of TCPC – Extracardiac conduit – Intra-arterial lateral tunnel • Preexisting atrial arrhythmias – Intraoperative ablation surgery including cryoablation • Atrial debulking • Correction of residual or recurrent lesions – AVVR, SAS, distorted pulmonary arteries Sejong General Hospital Surgical management protocol

• Intraoperative ablation surgery – Atrial reentry tachycardia or flutter

• Right-sided maze – Atrial fibrillation

• Maze–Cox III – Permanent pacemaker should be placed • Prophylactic arrhythmia ablation surgery – No data – However, extracardiac connections limit intracardiac access for subsequent arrhythmia therapy whether it is for catheter ablation or pacemaker implantation. Sejong General Hospital Fontan conversion

Author Year of Series size Mode of Arrhythmia FU (mo) Results Last FU status revision revision surgery McElhinney (1996) 1992-1995 7 EC 5 Not done 17 1 Early death Improved NYHA class, 4 IC 2 1 OHT PPM, 2 Kreutzer (1999) 1990-1994 8 LT 8 Not done 23 1 Early death Improved NHYA class, 5

Mavroudis (2001) 1994-2001 40 EC 32 Isthmus cryoablation 10 30 1 Late death (after OHT) NYHA class I/II, 37 LT 6 RA maze 16 2 OHT PPM, 38 Maze-Cox III 14 Setty (2002) 1997-2001 6 EC 6 Limited RA Maze 6 29 No mortality Improved NYHA class, 6 PPM, 6

Weinstein (2003) 1999-2002 10 EC 10 RA Maze 8 17 2 Early deaths NYHA class I/II, 8 Full Maze 2 PPM, 9 Sheikh (2004) 1997-2002 15 EC 11 Cryoablation 11 43 1 Late death Improved NYHA class, 14 LT 4 PPM 11 Kim (2005) 1996-2004 16 EC 11 Isthmus cryoablation 10 27 No mortality NYHA class I/II, 16 LT 5 RA Maze 3 PPM, 9 Morales (2005) 1997-2004 35 EC 19 RA Maze 28 29 2 Late deaths NYHA class I/ II, 32 LT 16 PPM, 29

* EC; extracardiac conduit, IC; intra-atrial conduit, LT; lateral tunnel, OHT; orthotopic heart transplantation, FU; follow-up, PPM; permanent pacemaker Sejong General Hospital Lessons learned

• Fenestration

– Unnecessary – Except patients with PLE • PLE

– Not good candidate • Aggressive management for atrial arrhythmias • Adequate timing Sejong General Hospital 이창하4 Timing ?

• Intervening during early stages of failing Fontan • At the first signs of atrial arrhythmias, conduit obstruction, significant atrial enlargement, or valvular dysfunction • Poor outcomes in marginal transplantation candidates (i.e. NYHA class IV) • Optimally, revision should be undertaken early in symptomatic patients before irreversible ventricular failure ensues 슬라이드 43 이창하4 timing인지 p549 suggested management protocol 인지 확실히 해야함 이창하, 2007-04-12 Sejong General Hospital Fontan conversion Sejong experience

• 2001-2005

• 6 patients underwent Fontan conversion

– AP Fontan (n = 5); lateral tunnel (n = 1)

– BT shunt (n = 1); classic Glenn (n = 1); bidirectional Glenn (n = 1)

– Conversion to extracardiac conduit Fontan in all Sejong General Hospital Fontan conversion Sejong experience

• Indication

– AP Fontan (n = 5)

• DOE, dilated RA & atrial dysrhythmia in all

• RA thrombi (n = 2); RPV compression (n= 1); Cyanosis (n = 1) – Lateral tunnel (n = 1)

• Total occlusion of lateral tunnel with hepatomegaly

• Sinus node dysfunction Sejong General Hospital Fontan conversion Sejong experience

Duration of Type of Age at F/U Fontan- Patient Diagnosis original conversion duration conversion Fontan (year) (year) (year)

1 TA IIb AP Fontan 12.5 18.9 5.4

DORV PS 2 AP Fontan 15.7 18.1 5.1 restrictive VSD

3 TA IIb AP Fontan 14.5 20.8 4.1

4 TA Ib Lateral tunnel 7.9 10.8 3.8

5 TA IIb AP Fontan 22.7 36.2 2.8

6 RV type UVH AP Fontan 18.8 24.6 1.4 Sejong General Hospital Fontan conversion Sejong experience

• Arrhythmia surgery

– Cryoablation (n = 2) / Modified right-sided maze (n = 3)

– PPM insertion (n = 3) Sejong General Hospital Fontan conversion Sejong experience

• Follow-up (median 3.9 yr, 1.4 – 5.4 yr)

– Improved functional class in all

– Sinus rhythm (n = 3), DDD pacing (n = 3) Sejong General Hospital

Heart transplantation Sejong General Hospital Reported outcomes of transplantation for Fontan failure

Study n Hospital mortality F/U (mo) Survival estimate Hsu (1995) 9 33% 23 67% Carey (1998) 9 33% 17 67% Lamour (1999) 8 38% 35 50% Michielon (2003) 6 67% ND ND Mitchell (2003, AATS) 15 7% 60 82% Gamba (2004) 14 14% 65 77%

* ND, data could not be derived from report Sejong General Hospital

•1993-2001, 17 Pediatric Heart Transplant Study centers •97 Fontan patient <18 yr of age listed

–mean interval from Fontan to listing; 4.9 ± 4.4 yr (range, 0 to 15 yr)

•22% < 6 months after Fontan •31% < 1 year •26% between 1 and 6 years •40% > 6 years •70 patients underwent heart transplantation

–mean interval from Fontan to transplantation; 5.7 ± 4.4 yr (range, 0.02 to 15.6 yr) Sejong General Hospital Risk factors for death while awaiting transplantation Sejong General Hospital Outcome of Listing for Cardiac Transplantation for Failed Fontan A Multi-Institutional Study

77% at 1 yr 73% at 3 yr 67% at 5 yr Sejong General Hospital Outcome of Listing for Cardiac Transplantation for Failed Fontan A Multi-Institutional Study

History of PLE Sejong General Hospital Pretransplant considerations in failing Fontan

• Multiple prior operations • Hepatic dysfunction • Cardiac & extracardiac vascular anatomy • Evaluation of the extent of ventricular dysfunction • Evaluation of pulmonary vascular disease & prediction of PVR – Acute right heart failure Sejong General Hospital Case - Ventricle dysfunction with dysrhythmia -

• M / 19 (1987) – Left isomerism, bilateral SVC, dextrocardia – UVH, common AV valve – IVC interruption with azygos continuity – s/p LMBT shunt (89) – s/p Kawashima operation (91) • Preoperatively – Moderate cyanosis – Pulmonary AV malformation, right – Severe ventricular hypertrophy with high VEDP (21mmHg) Sejong General Hospital Hepatic vein inclusion 06-12-30 Sejong General Hospital Fenestration POD #2 Sejong General Hospital Ventricular tachyarrhythmia Sejong General Hospital Ventricle dysfunction with tachyarrhythmia

POD #0 Bleeding control POD #6 ECMO support with Esmolol POD #2 LCO - fenestration (8mm) POD #10 ECMO weaning POD #17 Extubation POD #23 Transferred to general ward POD #52 Discharged with sinus rhythm Sejong General Hospital Conclusion

• Recently, early outcomes for Fontan procedures have been improving outstandingly.

• Fontan circulation has various limitations inherently, so adequate and timely interventions should be advocated in failing Fontan patients.

• Also, current practices of TCPC such as lateral tunnel or extracardiac conduit Fontan procedure should be carefully followed up.